Temperature is a ubiquitous environmental variable with major effects on physiology and behavior, and animals exhibit strong temperature-dependent orientation behaviors. However, the mechanisms that govern such orientation behaviors remain largely unknown. In this proposal, we propose to characterize the circuitry and the molecular mechanisms that guide this temperature-regulated behavior using molecular genetics in Drosophila. The aims of this proposal are to: Aim 1: Identify the neurons governing thermotactic behavior. We will identify and assess the function of neurons involved in thermotaxis by using genetic approaches to ablate and inhibit the function of specific neurons. Aim 2: Examine the molecular properties of regulators of thermotaxis and test the hypothesis that candidate thermosensory neurons act by triggering repulsion from extreme temperatures. Aim 3: Investigate the molecular basis of differences in themosensory behavior and candidate thermal sensors. Aim 4: Identify additional regulators of themotaxis using a combination of RNAi-based and conventional genetic screens. The goal of this research is to understand the molecular mechanisms and neural circuits that control animal behavior, by focusing on the molecules and neuronal pathways involved in sensing and responding to environmental stimuli. Our long-term experimental goal is to obtain a molecular and cellular explanation of how Drosophila undergoes directed migration guided by temperature differentials. Our results should provide insight into how animals process sensory information in order to discriminate between subtle gradations in sensory input, a topic of relevanceto human perceptual disorders like agnosia resulting from stroke or dementia and hallucination associated with mental illness. Our work will also enhance understanding of the basic mechanisms of temperature sensation. Temperature perception is highly relevant to the perception of pain, and our studies should provide insights into how such somatosensory information is sensed and processed.